Fig. 2: Spatial learning and memory flexibility are improved in Ccny KO mice.

a Schematic diagram for the Morris water maze (MWM) task, including original (Fig. 2b−f) and reversal (Fig. 2i−m) learning and visible platform (Fig. 2g, h) tests. b Learning curve of latency to platform during the original training sessions, Day 1 to 5, and latency to platform zone during the probe test session on Day 6 performed in the MWM after platform removal (gray shaded area). Data represent mean ± SEM. **P < 0.005, ***P < 0.0005 as indicated, Student’s unpaired t test. Data obtained from three cohorts. c Travel distance to platform zone during the probe test on Day 6 performed in the MWM after platform removal. *P < 0.05, Student’s unpaired t test. d, e The number of entries to (d) and time spent in (e) each quadrant during the probe test on Day 6 performed in the MWM after platform removal. TQ, target quadrant; LQ, quadrant left to the TQ; RQ, quadrant right to the TQ; OQ, quadrant opposite to the TQ. *P < 0.05, **P < 0.005, ***P < 0.0005 as indicated, Student’s unpaired t test. f The number of passing the platform zone during the probe test on Day 6 performed in the MWM after platform removal. *P < 0.05, Student’s unpaired t test. g, h Latency to platform during the visible sessions, V-Day 1 to 3 (g) and latency to platform zone during the visible probe test on V-Day 4 (h). Data represent mean ± SEM. ns, not significant, P = 0.223 (V-Day 1), P = 0.100 (V-Day 2), and P = 0.143 (V-Day 3) in (g), P = 0.203 in (h), Student’s unpaired t test. See also Supplementary Fig. S3. i−m Ccny KO mice exhibit an improved memory flexibility in reversal learning of the MWM task. i Latency to platform during the reversal learning training sessions, R-Day 1 to 3, and latency to platform zone during the reversal learning probe test on R-Day 4 (gray shaded area). Data represent mean ± SEM. *P < 0.05, **P < 0.005 as indicated, Student’s unpaired t test. Data obtained from three cohorts. j Travel distance to the platform zone during the reversal learning probe test on R-Day 4 performed in the MWM after platform removal. *P < 0.05, Student’s unpaired t test. k Time spent in each quadrant during the reversal learning probe test on R-Day 4 performed in the MWM after platform removal. Data represent mean ± SEM. PQ, previous target quadrant; TQ, target quadrant; LQ, quadrant left to the TQ; RQ, quadrant right to the TQ. *P < 0.05 as indicated, Student’s unpaired t test. l The number of entries to the previous target (PQ) and current target quadrant (TQ) during the reversal learning probe test on R-Day 4 performed in the MWM after platform removal. Data represent mean ± SEM. *P < 0.05, ***P < 0.0005 as indicated, Student’s unpaired t test. m The number of passing the platform zone during the reversal learning probe test on R-Day 4 performed in the MWM after platform removal. Data represent mean ± SEM. *P < 0.05, ***P < 0.0005 as indicated, Student’s unpaired t test. n Ccny KO mice exhibit improved memory flexibility in a delayed nonmatch to place (DNMTP) T-maze task. Data represent mean ± SEM of percentage of correct choices. *P < 0.05, Student’s unpaired t test. ^##P < 0.005 as indicated, repeated-measures two-way ANOVA, the effect of genotype, F (1, 29) = 9.874. See also Supplementary Fig. S4. o Memory flexibility in GluN2B-C456Y-mutant mice is comparable to the littermate WT in a DNMTP T-maze task. Data represent mean ± SEM of percentage of correct choices. Student’s unpaired t test. ns, not significant, repeated-measures two-way ANOVA, the effect of genotype, F (1, 15) = 2.244. See also Supplementary Fig. S4.